GRADING PROSTATE CANCERS

1. GLEASON
GRADING & SCORING
DR. ABHINAV GOLLA
MEDICURE DIAGNOSTICS AND
RESEARCH CENTER
Vijayanagar colony, HYDERABAD,
TELANGANA.

2. INTRODUCTION
PATTERNS 1 – 5
GLEASON SCORING
REPORTING IN DIFFERENT SPECIMENS
TERITIARY PATTERN IN BIOPSIES
MODIFICATION IN GLEASON SCORING
NEW SCORING SYSYTEM
VALUE OF GLEASON SCORING

3. Introduction
 Donald F. Gleason in 1966 created a unique grading
system for prostatic carcinoma.
 In 1974 and 1977, he provided additional comments
concerning the application of the Gleason system.
 Since its 1ST proposal, the Gleason grading system has
been accepted as one of the most powerful prognostic
indicators in prostate cancer throughout the world.

4. Introduction
 Gleason grading depends solely on architectural
patterns of the tumor.
 The grade is defined as the sum of the two most
common grade patterns and reported as the
Gleason score.
 Synonyms for “Gleason score” are “combined
Gleason grade” and “Gleason sum”.

5. Gleason Patterns
 As described by Gleason, the grading of
prostate carcinoma has to be performed under
low magnification (4x or 10x objective).
 One should not initially use the 20x or 40x
objectives to look for rare fused glands or a few
individual cells seen only at higher power which
would lead to an overdiagnosis of high Gleason
patterns.

6.  The drawing showing original Gleason
grading well formed discrete glands in
pattern 1 to poorly formed with necrosis
or no gland formation in pattern 5.

7. Gleason Pattern 1
 Gleason pattern 1 tumor is a circumscribed nodule.
 composed of uniform, single, separate, closely packed
glands.
 Gland spacing usually does not exceed one gland diameter.
 Gleason pattern 1 is very uncommon.
 A Gleason score of 1+1=2 must be considered as an
extremely rare exception regardless of the type of
specimen.

8.  The Gleason system predated the use
of immunohistochemistry.
 It is likely that with immunostaining for
basal cells many of Gleason’s original
1+1=2 adenocarcinomas of the
prostate would today be regarded as
adenosis (atypical adenomatous
hyperplasia).

10. Gleason Pattern 2
 The tumor is still fairly circumscribed,
however at the edge of the tumor nodule
there can be minimal extension by
neoplastic glands into the surrounding non-
neoplastic prostate.
 The glands are more loosely arranged and
not quite as uniform in comparison with
Gleason pattern 1.

11.  The Gleason pattern 1 and Gleason pattern 2 glands
tend to be larger than intermediate grade
carcinomas.
 Contrary to the original Gleason system, cribriform
glands are not allowed in pattern 2. Typically, both
Gleason pattern 1 and pattern 2 carcinomas have
abundant pale eosinophilic cytoplasm.

13. Gleason Pattern 3
 The vast majority of Gleason pattern 3 is
composed of single glands that show marked
variation in size and shape.
 The neoplastic gland size is usually smaller than
seen in Gleason pattern 1 or 2.
 Gleason pattern 3 tumor infiltrates in between
non-neoplastic prostate acini.

14.  In contrast to Gleason pattern 4, the glands in
Gleason pattern 3 are distinct units so that one can
mentally draw a circle around well-formed individual
glands.
 Gleason grading as stated above has to be applied
at low power objective.
 The presence of a few poorly formed glands at high
power is still consistent with Gleason pattern 3.

17. Gleason Pattern 4
 Pattern 4 has become significantly expanded beyond
Gleason’s original description of tumors with clear
cytoplasm that resembled renal cell carcinoma.
 Gleason pattern 4 today consists of large irregular
cribriform glands or fused, ill-defined glands with poorly
formed glandular lumina.
 Glands are no longer single and separate as seen in
patterns 1 to 3.

18.  A tangential section of Gleason pattern 3 may produce a
minute cluster that gives false impression of ill-defined
glands with inconspicuous lumina, and thus may lead to
misdiagnosis as Gleason pattern 4.
 Very small, but still well formed glands are within the
spectrum of Gleason pattern 3.

19.  Hypernephromatoid pattern is an uncommon
variant of Gleason pattern 4.
 Here, tumor is composed of clear cells and reminds
renal cell carcinoma microscopically.

24. Gleason Pattern 5
 In Gleason pattern 5, tumor shows no glandular
differentiation.
 Instead it is composed of solid sheets, cords, trabeculae
or single cells.
 Cribriform or solid nests of tumor with central comedo
necrosis are also classified under Gleason pattern 5.

25.  One must be stringent as to the definition of
comedonecrosis.
 Luminal eosinophilic secretions may be misinterpreted as
comedonecrosis.
 The presence of intraluminal necrotic cells and/or
karyorrhexis is required especially in the setting of
cribriform glands.

26.  Tumors with comedonecrosis generally have high
nuclear grade often with brisk mitotic activity.
 Gleason stated that “A small focus of disorganized
cells did not change a pattern 3 or 4 tumor to
pattern 5”.

30. GLEASON SCORING
 Depends solely on architectural patterns of the tumor.
 The grade is defined as the sum of the two most
common grade patterns.
 Both the primary (predominant) and the secondary
(second most prevalent) architectural patterns are
identified and assigned a number from 1 to 5, being 1
the most differentiated and 5 the least differentiated.

31.  When a tumor has only one histologic pattern, the primary and
secondary patterns are given the same number.
 Thus Gleason scores range from 2 (1+1=2), which are the tumors
uniformly composed of Gleason pattern 1, to 10 (5+5=10), which
represents totally undifferentiated tumors.
 A tumor that shows predominant Gleason pattern 3 with a lesser
quantity of Gleason pattern 5 has a Gleason score of 8 (3+5=8), as
does a tumor that is predominantly Gleason pattern 5 with a lesser
amount of Gleason pattern 3 (5+3=8).

32.  Both primary and secondary Gleason patterns have to be
assigned even for the cancer focus that is minute on a needle
biopsy.
 When the pathologist signs out a case as “Gleason grade 4” to
mean that the tumor is high grade (i.e. Gleason pattern 4), the
urologist may interpret it as Gleason score of 4 (i.e. Gleason
grade 2+2=4).
 Combined Gleason score prevents this confusion.

33. Reporting
 Histologic grade should be reported for untreated
adenocarcinoma in every prostatic tissue sample.
 The Gleason grade should be utilized and primary
pattern plus secondary pattern equals score
should be recorded.
 Another scheme may be reported in addition to
Gleason grade, but Gleason grade should always
included in report.

34. TYPES OF SPECIMEN
 Needle biopsy cores(TRUS): Indicated in patients
with suspicious findings on digital rectal
examinations or PSA >4.0ng
 TURP chips: indicated in BPH if symptoms are
not relieved by medication.
 Radical prostatectomy: Early stage of prostate
cancer.

35. reporting
For Needle biopsy cores:
 Gleason scores for each recognizable core have to
reported separately irrespective of whether the cores
are individually submitted (in individual container
signifying specific anatomic location), or submitted
together.

36. reporting
 When there are multiple cores per container, they often
fragment. If tissue fragmentation makes grading of
individual cores difficult, the effort should be exerted to
identify and provide information on the core with the
highest Gleason score.
 When the cores are extremely fragmented, it becomes
impossible or potentially misleading to give a Gleason score
on small tissue pieces. In these cases only an overall score
for that container must be given.

37. reporting
For Radical prostectomy specimens:
 Tumor size should be reported as the percentage
of the cancer in prostate.
 Additionally dominant nodule should be
measured in two dimension and number of blocks
involved by tumor over total number of blocks
submitted should be mentioned.

38. reporting
 Gleason grade should be assigned in standard fashion,
with primary and secondary Gleason pattern and total
score.
 A tertiary high-grade, when present, should definitely be
reported as this has an impact on prognosis.
 The evidence based recommendation is to keep the
original Gleason score with a notation on the presence
of a tertiary high grade component.

39. reporting
For TURP chips:
 TURP is common urologic procedure that is used for surgical
management of BPH.
 The quantity of tissue chips received in lab varies.
 The recommendation by College of American
Pathologists(CAP) require submission of specimen weighing
12 gm or less in their entirely.

40. reporting
 For the specimen greater than 12 g, initial 12 g should be
submitted and then 1 block for every 5 g may be
submitted.
 The CAP committee recently recommended that “if an
unsuspected carcinoma is found in the tissue submitted
and it involves less than 5% or less, remaining tissue
should be submitted for examination.”

41. Tertiary pattern in needle biopsies
 As being different than radical prostatectomy, these tumors
on needle biopsy should not be graded simply by summing
the primary and secondary pattern.
 When the worst Gleason grade is the tertiary pattern, it
should influence the final Gleason score and must replace the
secondary grade in the Gleason score calculation formula.

42.  Example: a case with primary Gleason pattern 3, secondary
pattern 4, and tertiary pattern 5 should be assigned a
Gleason score of 8 (3+5=8) (the primary pattern + the
highest grade =score).
 Presence of both Gleason patterns 4 and 5 on needle
biopsy most likely indicates an overall high grade tumor,
and that its limited extent reflects a sampling issue.

43. Modifications in Gleason System
 Since the introduction of Gleason grading system, many
aspects of prostate cancer have changed, including:
The use of PSA testing,
transrectal ultrasound-guided prostate needle biopsy
with greater sampling,
immunohistochemistry for basal cells changing the
classification of prostate cancer,
discovery of new prostate cancer variants (ie.
pseudohyperplastic, foamy gland, mucinous, ductal).

45. Limitations of current system
 Gleason scores 2 to 5 are currently no longer
assigned and certain patterns that Gleason
defined as a score of 6 are now graded as 7, thus
leading to contemporary Gleason score 6 cancers
having a better prognosis.

46. Limitations of current system
 In practice, the lowest score now assigned is 6, although it
is on a scale of 2 to 10.
 This leads to a logical yet incorrect assumption on the part
of patients that the cancer on biopsy is in the middle of the
grade scale, compounding the fear of a cancer diagnosis.
 This leads to an expectation that definite treatment is
always necessary.

47. Limitations of current system
 Combining Gleason scores into 3-tier grouping (6,
7, 8-10) is used most frequently for prognostic
and therapeutic purposes, despite 3 + 4 = 7
versus 4 + 3 = 7 and 8 versus 9 to 10 having very
different prognoses.

48. Development of new grading system
 As a result of first to problems mentioned earlier, it has
been questioned if Gleason score 3+3=6 should retain
the designation of cancer or be labelled as a indolent
lesion of epithelial origin to avoid fear and
overtreatment.
 So, 5 grade group system was established which
correlates well with prognosis of the disease and
excludes Gleason score 2 to 5 defining Gleason score 6 as
a lowest grade.

49. New grading system
Grade Group Pattern definition 5 year
survival
rate
Grade group 1(G.S ≤6 ) Only individual well-formed discreet glands 96%
Grade group 2(G.S 3 + 4 =
7 )
Predominantly well-formed glands with lesser
component of poorly
formed/fused/cribriform glands
88%
Grade group 3(G.S 4 + 3 =
7 )
Predominantly poorly
formed/fused/cribriform glands
with lesser component of well-formed glands
66%
Grade group 4(G.S 8 ) Only poorly formed/fused/cribriform glands 48%
Grade group 5(G.S 9 - 10 ) Lacks gland formation/ necrosis with or
without poorly formed glands
26%

50. Benefits of new grading system
1. Provides mare accurate grade stratification than current
application of the Gleason system.
2. It is simple with 5 grade groups as opposed to 25 scores
depending on various Gleason grading patterns
combination.
3. The lowest grade in the new system is 1 as opposed to 6
in the Gleason system.

51. Value of gleason scoring
 While the decision for the definitive therapy
of prostatic carcinoma is based on multiple
factors including the clinical stage, patient
age, preoperative PSA, patients general
health, life expectancy, etc., the Gleason grade
in needle biopsy is another variable that can
potentially help stratify patients into different
therapeutic modalities.

52.  Gleason score on biopsy correlates with all of the
important pathologic parameters at radical
prostatectomy, with prognosis after radical
prostatectomy (recurrence and survival) and with
outcome following radiotherapy as well as serum
pre-op PSA levels and many molecular markers.

53. Value of gleason scoring
 Gleason score 7 tumors behave significantly worse than
Gleason score 5-6 tumors and do better than Gleason
score 8-10 tumors.
 If one wants to combine Gleason scores on biopsies into
groups the following categorization is reasonable:
Gleason score 2-4 (well-differentiated);
Gleason score 5-6 (moderately differentiated);
Gleason score 7 (moderately-poorly differentiated);
Gleason score 8-10 (poorly differentiated).

54. Value of gleason scoring
 Grade is one of the most influential factors used to
determine treatment for prostate cancer.
 Whereas some younger men with limited amounts of
Gleason score 5-6 on needle biopsy and low PSA values
may be followed expectantly (“watchful waiting”), almost
all men with Gleason score 7 tumor will be treated more
definitively.
 The presence of a Gleason pattern 4 (score ≥7) dictates, in
most cases, prompt intervention.

55. Thank you

56. References
 Epistein JI, Zelefsky MJ,Sjoberg DD et al. A new contemporary
prostate cancer grading system 2016
 Dilek Ertoy Baydar, Jonathan i. Epstein, Gleason grading system,
modifications and additions to the original scheme. Turkish journal of
pathology:cilt/vol. 25, no. 3, 2009; sayfa/page 59-70.
 Oleksandr N. Kryvenko and Jonathan I. Epstein (2016) Prostate Cancer
Grading: A Decade After the 2005 Modified Gleason Grading System.
Archives of Pathology & Laboratory Medicine: October 2016, Vol. 140,
No. 10, pp. 1140-1152
 Classification of tumours of the prostate WHO 2016
 2015 ISUP/ 2016 WHO revised gleason diagram.